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A review on transfer factor an immune modulator

DOI:10.1016/j.dit.2013.04.002
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Marimuthu Krishnaveni at Periyar University
Marimuthu Krishnaveni
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Aim To understand what is transfer factor and its significance in stimulating immune system which is necessary for the general maintenance of health. Methods Articles were collected from net sources. Results Basics, mechanism of action, safety aspects of transfer factor were discussed in this review. Diseases showing positive result with transfer factor treatment are tabulated. Conclusion From this it is concluded that it is a dialyzable, active protein initiator molecule able to transfer cell mediated immunity from healthy donor to recipient who is non-immune thus keeping one away from infection.
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Review Article
A review on transfer factor an immune modulator
Marimuthu Krishnaveni*
Department of Biochemistry, Periyar University, Salem 11, Tamil Nadu, India
article info
Article history:
Received 19 March 2013
Accepted 30 April 2013
Keywords:
Cell mediated immunity
Cytokines
Diseases
Molecule
Passive transfer
abstract
Aim: To understand what is transfer factor and its significance in stimulating immune
system which is necessary for the general maintenance of health.
Methods: Articles were collected from net sources.
Results: Basics, mechanism of action, safety aspects of transfer factor were discussed in this
review. Diseases showing positive result with transfer factor treatment are tabulated.
Conclusion: From this it is concluded that it is a dialyzable, active protein initiator molecule
able to transfer cell mediated immunity from healthy donor to recipient who is non-im-
mune thus keeping one away from infection.
Copyright ª2013, JPR Solutions; Published by Reed Elsevier India Pvt. Ltd. All rights
reserved.
1. Introduction
Transfer factor is a natural, non-species specific, tiny, small
peptides of 3500e6000 kDa in molecular weight, transparent,
light yellow fluid having pH 6.5e7.0, composed of oligor-
ibonucleotides attached to a peptide molecule that are
inherent in all animal bodies, said to be non-allergic because
of their small size and act as immunomodulator, RNA might
provide a cytophilic property. Dr. Kirkpatrick
1
identified
highly conserved region of amino acids in transfer factor that
are able to bind to the target cells with high affinity. Higher
tyrosine, glycine content are present in some variants. The
first milk in all mammalian mother called colostrums, a god’s
gift which gives passive immunity to newborn babies, has
been proven to contain transfer factor, non-antigen specific
moieties present in colostrum might contribute for the bene-
ficial outcome in patients by stimulating their immune system
non-specifically and are universally effective. H. Sherwood
Lawrence demonstrated this passive transfer of immunity in
1949.
2,3
It can also be obtained from immune donor
lymphocyte who is able to transfer cell mediated immunity to
a non-immune recipient. This helps to act against bacterial,
viral, parasitic infection, autoimmune diseases, diabetes,
autism, infertility, psoriasis, retinitis pigmentosa, asthma,
cancer.
4e6
The positive responses are confirmed through
various tests such as delayed hypersensitivity test on skin,
response to alloantigen, specific and non-specific mitogen,
type of T cell, NK cell activity, cytokines activity. Since,
transfer factors are acquired in our bodies through natural
immune system and able to perform catalytic function in
immune system triggering effect without getting consumed,
4
this review aimed to provide briefly its mechanism of action
once synthesized, immunological role in aiding cell mediated
immunity as it is having extraordinary benefits.
2. Sources
Birds have transfer factor inside their eggs providing a library
of immune system and identifiers to make out the attacking
* Tel.: þ91 9894829823 (mobile).
E-mail address: krishnavenim2011@gmail.com.
Available online at www.sciencedirect.com
journal homepage: www.elsevier.com/locate/dit
drug invention today 5 (2013) 153e156
0975-7619/$ esee front matter Copyright ª2013, JPR Solutions; Published by Reed Elsevier India Pvt. Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.dit.2013.04.002
pathogen.
7
Transfer factors are synthesized form animal,
human sources by injecting with certain pathogen to produce
specific transfer factor. Transfer factor generated using
human blood are human derived, cow and mouse spleen are
bovine, murine derived. Viza and his coworkers in 1974
observed that transfer factor with known antigenic specific-
ities can be generated from LDV/7 lymphoblastoid cell line.
8
The dialyzable transfer factors have onset period as hours
and able to maintain its effectiveness for five years. Transfer
factor can be purified by high performance liquid chroma-
tography and column chromatography.
3. Mechanism of action
Transfer factor lack viable cells that play a role in graft versus
host reaction, not immunogenic, contain no histocompatibil-
ity antigens.
9,10
Natural immune response is a causative factor
for the production of transfer factor and they are produced
within T helper cells (Fig. 1), once released, the immune sys-
tem activity is influenced in several ways and studied by other
cells involved in immune system which indicates, that T
helper cells are active in fighting against the pathogen,
thereby stimulating the production of new helper T cells,
Natural killer cells, macrophages, cytotoxic T cells. Thus,
marching close to the target most probably by influencing the
expression of antigen receptors on cells. Increased Th1 in turn
repress the production of Th2 and its cytokines like IL-4, IL-5,
IL-6, and IL-13. A remarkable feature of transfer factor is
eliciting multiple, opposing function
11,12
or bio feedback
mechanism by antigen specific, inducer, suppressor/regula-
tory fraction contained in it. Here, antigen specific fractions
aid the function of recognizing and memorizing pathogenic
organisms in a more faster manner. Secondly, inducer frac-
tion increases the antigenic stimulus whereas, suppressor
fraction act by releasing IL-10, an inhibitory cytokine from Th2
cells, playing a vital role in controlling immune over reactions,
mistargeted reactions in the development of autoimmune
disorders. Kirkpatrick demonstrated that in vivo administra-
tion of transfer factors to mice, afford the recipients spleen
cells with the property of responding to target antigen in vitro
by secreting gamma interferon,
13
a product of Th1 cells, IL-2,
TNF-alpha thereby ensuring the development of cell medi-
ated immunity. While stimulating cell mediated immunity, it
does not increases antibody secretion as well its responses
against the same specific antigen. So, transfer factors develop
cell mediated responses in patients who are suffering from
immunodeficient, infectious disease, as well as in disorder
with certain anergies. Maturation of naive T cells as well as
increased cell mediated immunity are regulated by thymic
factors. It is agreed that transfer factor is more effectual in
educating naive cells about the approaching danger. So, in the
treatment of mild thymic primary immunodeficiency, both
thymic and transfer factors are suggested.
14,15
Several factors
that decrease cell mediated immunity, Th2 supremacy are
age, cytotoxic cancer treatments, stress developed after sur-
gery, metastatic diseases.
16
Thus, cell mediated immunity
plays a major role in judging the morbidity and mortality
above sixty years.
4. Transfer factor and diseases
The immune system is a versatile system encompasses more
than a trillion cells, weighing about 1 kg and helps in recog-
nizing, fighting, remembering invading pathogens. Each
pathogen can bring out transfer factor, atleast one transfer
factor is created for every piece of pathogen that the immune
system faces. Transfer factors influence the activities of
various immune components and also regulate cytokines.
17
Imbalances in the production of transfer factor lead to the
development of rheumatoid arthritis, cancer, Alzheimer’s,
heart disease, hepatitis and so on. The time taken for com-
plete development of immature immune response/delayed
hypersensitivity is 10e14 days, but transfer factor induces an
immune response in within 24 h.
18
IMREG I and IMREG II
19
help in bringing out balanced immune system. Fudenberg’s,
three important measures that have to be taken care are
antigenic specificity, strength of the extract and recipients
immune status
20
and also the right dose. Vetto et al reported
that patients in advanced cancer stages were not able to
respond when they were treated with antigen induced
lymphocyte transformation.
21
Few diseases that were studied
with transfer factor are depicted in Table 1.
5. Stability and safety of transfer factor
Transfer factor can resist freezing, withstand treatment with
DNase, pancreatic RNase, and trypsin
34
but destroyed by
snake venom phosphodiesterase. No bad side effects have
been reported so far with transfer factor,
35
and valuable when
administered orally as well as by injection.
17,36
Long-term oral
administration is convenient,
37
safe
38,39
and easily accepted
37
by infants, elderly people who are at the risk for numerous
infections. Dresseler and Rosenfield
40
reported, that heat
lability of transfer factor depends on the melting of a double
stranded nucleic acid, full activity was retained at 80 C, above
90 C destroyed the activity, had an intermediate activity at
85 C but stable to cold and consequently, able to retain its
biological activity even after storing at 20 Cto70 C forFig. 1 eShowing synthesis of transfer factor.
drug invention today 5 (2013) 153e156154
several years. Since, transfer factors are derived from blood
products it will be safe to check for HIV/AIDS/hepatitis to get
rid of blood borne diseases.
6. Conclusion
The life we are living must be healthy as long as we are.
Everyone is aware, that our immune system gets activated
only when we are exposed to infection. Hence, greater the
exposure, better the immunity. To conclude, transfer factor is
an immune enhancing molecule produced naturally by our
immune system aiding immunological memory of recipient. It
is not a drug or vitamin to cure our illness but it acts as a
channel to our immune system. So, a balanced immune sys-
tem is attained. Eventhough, they found to be useful, the
success rate varies depending upon the preparation of trans-
fer factor, the right dose selected, the potency, the degree of
illness and duration of infection.
Conflicts of interest
The author has none to declare.
Acknowledgement
The author whole heartedly thank JPR solution for their partial
contribution in publishing this article without which this
would have not been possible.
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Table 1 eShowing few diseases studied with transfer factor.
Diseases showing positive result on
treatment with transfer factor
Effects References
Osteosarcoma Increased cell mediated cytotoxicity Fudenberg 1976
22
Varicella with acute leukaemia in children Steele et al, 1980
23
Herpes simplex virus Improved T cell function Steele et al, 1976
24
Viza et al, 1986
25
WiskotteAldrich syndrome Increased C3 level returned to normal, no new infection,
absence of eczema
Levin et al, 1970
26
Glioma Reduces the tumour size, and increases CD2þ, CD4þ,
CD8þand NK cell counts, apoptotic tumour cells
Pineda et al, 2005
27
Prostate cancer Higher survival rates Pizza et al, 1996
28
HIV Increased levels of helper T cells and cytotoxic T cells Granitov et al, 2002
29
Lung cancer Longer survival Pilotti et al, 1996
30
Hepatitis C Stimulates Th1, which helps in clearing of viral particles
31,32
Chronic mucocutaneous candidiasis Restored cellular immunity
33
drug invention today 5 (2013) 153e156 155
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drug invention today 5 (2013) 153e156156
... There is evidence that TFs consist of short chains of amino acids with small pieces of ribonucleic acid (RNA) attached [16,17]. The RNA is probably related to a cytophilic property and the specificity of the TF [18], as the absence of the oligoribonucleotide linked to the amino termination of peptides results in loss of activity [7]. ...
... The length of the peptide chain of TFs is still under debate; there are reports of 17 or 18 amino acids present in TF [19,20], with high tyrosine and glycine content [18], but given the molecular weight of the fractions, they could be even bigger molecules with 24 amino acids or more. Especially since, the molecular weight of tryptophan (the heaviest amino acid), for example, is more than 200 Da [21]. ...
... It also needs to be taken into consideration that by nature, TFs extracts are complex mixtures, containing a high number of different TFs, and not just one single chemical entity [22]. In contrary to Imuno TF ® , other commercially available traditional TF extracts are generally obtained from cow colostrum (which can cause allergic reactions in other species due to the presence of immunoglobulins [23]), bird's egg yolks, or other tissue obtained from suitable animals [18,22]. Until now, little is known about the exact chemical composition of the TFs. ...
Characterization and Safety Profile of Transfer Factors Peptides, a Nutritional Supplement for Immune System Regulation
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Imuno TF® is a nutritional supplement composed of isolated transfer factors (TF) from porcine spleen. It is composed of a specific mixture of molecules that impact functions of the biological systems and historically is linked to the immune system regulation. In this study, we demonstrate for the first time its proteomic analysis, nutritional composition, and safety profile in terms of mutagenic potential and acute oral dose (LD50). The obtained analysis indicated the product is a complex set of oligo- and polypeptides constituted of 163 different peptides which can potentially act on multiple mechanisms on the immune system pathways. The chemical composition showed low fat and low sugar content, saturated fatty acids-free, and the presence of 10 vitamins and 11 minerals. No mutagenic effect was observed, and the LD50 was 5000 mg kg−1 body weight. This accounts for a safe product to be used by the oral route, with potential benefits for the immune system.
View
... Transfer factors are low molecular weight polypeptides fractions obtained from natural sources such as colostrum, egg yolks, or porcine spleen. 164 Specifically, it is derived from T-lymphocytes, and the immunomodulatory properties of TF have been well documented. It has been used to combat viral infections successfully. ...
... It has been used to combat viral infections successfully. 164 ...
Attenuating the Effects of Novel COVID-19 (SARS-CoV-2) Infection-Induced Cytokine Storm and the Implications
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The COVID-19 pandemic constitutes an arduous global health challenge, and the increasing number of fatalities calls for the speedy pursuit of a remedy. This review emphasizes the changing aspects of the COVID-19 disease, featuring the cytokine storm's pathological processes. Furthermore, we briefly reviewed potential therapeutic agents that may modulate and alleviate cytokine storms. The literature exploration was made using PubMed, Embase, MEDLINE, Google scholar, and China National Knowledge Infrastructure databases to retrieve the most recent literature on the etiology, diagnostic markers, and the possible prophylactic and therapeutic options for the management of cytokine storm in patients hospitalized with COVID-19 disease. The causative agent, severe acute respiratory coronavirus-2 (SARS-CoV-2), continually threatens the efficiency of the immune system of the infected individuals. As the first responder, the innate immune system provides primary protection against COVID-19, affecting the disease's progression, clinical outcome, and prognosis. Evidence suggests that the fatalities associated with COVID-19 are primarily due to hyper-inflammation and an aberrant immune function. Accordingly, the magnitude of the release of pro-inflammatory cytokines such as interleukin (IL)-1, (IL-6), and tumor necrosis alpha (TNF-α) significantly differentiate between mild and severe cases of COVID-19. The early prediction of a cytokine storm is made possible by several serum chemistry and hematological markers. The prompt use of these markers for diagnosis and the aggressive prevention and management of a cytokine release syndrome is critical in determining the level of morbidity and fatality associated with COVID-19. The prophylaxis and the rapid treatment of cytokine storm by clinicians will significantly enhance the fight against the dreaded COVID-19 disease.
View
... Transfer factors are low molecular weight polypeptides fractions obtained from natural sources such as colostrum, egg yolks, or porcine spleen. 164 Specifically, it is derived from T-lymphocytes, and the immunomodulatory properties of TF have been well documented. It has been used to combat viral infections successfully. ...
... It has been used to combat viral infections successfully. 164 ...
Review: Attenuating the Effects of Novel COVID-19 (SARS-CoV-2) Infection-Induced Cytokine Storm and the Implications
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Full-text available
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The COVID-19 pandemic constitutes an arduous global health challenge, and the increasing number of fatalities calls for the speedy pursuit of a remedy. This review emphasizes the changing aspects of the COVID-19 disease, featuring the cytokine storm's pathological processes. Furthermore, we briefly reviewed potential therapeutic agents that may modulate and alleviate cytokine storms. The literature exploration was made using PubMed, Embase, MEDLINE, Google scholar, and China National Knowledge Infrastructure databases to retrieve the most recent literature on the etiology, diagnostic markers, and the possible prophylactic and therapeutic options for the management of cytokine storm in patients hospitalized with COVID-19 disease. The causative agent, severe acute respiratory coronavirus-2 (SARS-CoV-2), continually threatens the efficiency of the immune system of the infected individuals. As the first responder, the innate immune system provides primary protection against COVID-19, affecting the disease's progression, clinical outcome, and prognosis. Evidence suggests that the fatalities associated with COVID-19 are primarily due to hyper-inflammation and an aberrant immune function. Accordingly, the magnitude of the release of pro-inflammatory cytokines such as interleukin (IL)-1, (IL-6), and tumor necrosis alpha (TNF-α) significantly differentiate between mild and severe cases of COVID-19. The early prediction of a cytokine storm is made possible by several serum chemistry and hematological markers. The prompt use of these markers for diagnosis and the aggressive prevention and management of a cytokine release syndrome is critical in determining the level of morbidity and fatality associated with COVID-19. The prophylaxis and the rapid treatment of cytokine storm by clinicians will significantly enhance the fight against the dreaded COVID-19 disease.
View
... Transfer imunitas passive juga diperoleh dari limfosit donor imun yang mampu mentransfer imunitas yang diperantarai sel kepada host non-imun. Hal ini dapat beraksi untuk melawan infeksi bakteri, virus, parasit, penyakit autoimun, diabetes hingga kanker (Krishnaveni, 2013). ...
Studi kasus : Mastitis kronis non-suppuratif pada anjing poodle usia 9 tahun
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... Transfer factor (TF) is a low molecular weight lymphocyte extract which can transfer antigen specific cell mediated immunity to T lymphocytes. Apart from its use in infections, specifically viral infections like herpes, it can be used in a wide array of conditions like malignancies, allergies, immunodeficiency and autoimmunity mediated conditions (37). TF increases the expression of interferon (IFN)-γ and RANTES (regulated on activation, normal T cell expressed and secreted, CCL5), while it decreases the expression of osteopontine (38). ...
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Children with nephrotic syndrome (NS) develop complications due to either the disease state or its treatment. Infections, thromboembolism and acute kidney injury are the most common complications in children with NS. Several studies in children with NS have reported that urinary tract infections, upper respiratory tract infections, peritonitis and sepsis are the most commonly reported infections. Infection is one of the common triggering factors for relapse, and prophylaxis against infections is required in patients unresponsive to steroids or with frequently relapsing disease. In this review article, we summarize the strategies for prevention of infections in NS. The most commonly studied drug for the prevention of infection in NS is intravenous immunoglobulin G (IVIg), while other drugs include thymosin, oral transfer factor, Bacillus Calmette-Guérin (BCG) vaccine, mannan peptide tablet, polyvalent bacterial vaccine and Chinese herbal medications (Tiaojining and Huangqui granules). Several vaccination programs including pneumococcal, influenza A, varicella and measles have been effective in the prevention of infections in nephrotic children. However, established measures for preventing infections in nephrotic children are lacking, and to draw any conclusion, randomized controlled trials are required.
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... Transfer factors influence the activities of various immune components and also regulate cytokines. The time taken for complete development of immature immune response/delayed hypersensitivity is 10-14 days, but transfer factor induces an immune response within 24 hours (Krishnaveni, 2013). Transfer factor have many therapeutic and prophylactic applications, especially in diseases where cell-mediated immunity plays a major role (García-Hernández et al., 2014). ...
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Research and development of means for effective prevention and treatment of diseases in animals are one of the priorities for modern veterinary science. Means based on the transfer factor are quite promising to solve these problems. One of the stages of obtaining a qualitative transfer factor specific to a particular disease is the sensitization of the body of donor animals. The purpose of this work was to investigate the blood biochemical parameters of donor cows after sensitization according to different schemes. The experiments were performed on cows of the Ukrainian black-spotted dairy breed, aged 4–5 years. Sensitization of pregnant cows was performed 1–1.5 months before calving with a concentrated formol-alum vaccine against salmonellosis of calves manufactured by the Kherson Biofactory. The vaccine was administered to the animals of the first experimental group one month before calving, one-time in a dose of 10 ml. Animals of the second experimental group 1.5 months before calving were two-time vaccine administered with an interval between injections of 10 days in doses of 10 and 15 ml. Studies have shown that in donor cows, which were two-time vaccine administered, there was an increase in hemoglobin content by 13% (P<0.05). There was also a decrease in glucose and creatinine content by 13–28% (P<0.05–0.01) in the blood serum of pregnant cows, which did not depend on the sensitization scheme, and a tendency to a decrease in total protein content. Regardless of the sensitization scheme of cows, an increase in serum aminotransferase activity was observed by 1.3–1.5 times (P<0.05–0.001), and if alanine aminotransferase activity increased mainly with a single injection of the vaccine, then aspartate aminotransferase activity was more intensively increased after a two-time vaccine administration. There was a slight decrease in сalcium (by 5–9%) and phosphorus (by 2–3%) content and an increase in potassium content (by 2–5%) in the blood serum of pregnant cows two weeks after vaccine administration regardless of the sensitization scheme.
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... This can be related to macrophage activation by Imuno TF ®28, 29 IL-1 and TNF-. 28,29,32,[42][43][44] In addition, Imuno TF ® positively regulates Th1 cytokines, while decreases the release of Th2 cytokines (IL-4, IL-5, IL-6, IL-13). 45 This is relevant once there is evidence that the Th2 overresponse are linked to bronchoconstriction, dyspnea and exacerbations of allergic airways diseases. ...
Evolution of COVID-19 patients treated with ImmunoFormulation, a combination of nutraceuticals to reduce symptomatology and improve prognosis: a multi-centred, retrospective cohort study
Preprint
Full-text available
  • Dec 2020
Background Although a vast knowledge has already been gathered on the pathophysiology of COVID-19, there are still limited, non-optimal treatment options. In this context, agents that can act on prophylaxis or as adjuvants to the therapies are of high value. Methods In this paper, we describe a multicentre, retrospective, observational study to describe the course of SARS-CoV-2 disease in patients treated with ImmunoFormulation (IF), an add-on therapy developed to decrease duration of clinical symptoms. In parallel, a group of patients that did not receive IF was used for comparison (using standard of care treatment). A total of 39 patients were evaluated for their recovery rate, general symptoms and their severity, and adverse reactions. Results Throughout the observational period, 90% of patients recovered in the IF cohort and 47.4% in the Control cohort (p=0.0057). From the symptoms with statistically significant differences, the duration of symptoms (i.e., the time to recover from it) was shorter in the IF cohort than in control cohort (in days, average), especially for fever (2.25 x 21.78), dry cough (4.38 x 24.00), dyspnoea (3.67 x 20.00), headache (2.00 x 26.50), diarrhoea (5.25 x 25.25), and weakness (1.92 x 23.30). Conclusions This demonstrates a potential promising role of IF as adjuvant therapy on the evolution of symptomatology to COVID-19 patients.
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INDIVIDUAL FEATURES OF THE BOVINE COLOSTRUM PROTEOME
Conference Paper
Full-text available
  • Aug 2023
One of the urgent tasks of biotechnology is obtaining of biologically active compounds of natural origin. Colostrum is a promising object for solving such problems, since it contains a large number of various natural compounds. Bovine colostrum proteins are of particular interest in this respect. As is known, most farm animals (calves, foals, piglets, camels) are born agammaglobulinemic [1] and receive passive immunity due to the first intake of colostrum, which is extremely rich not only in immunoglobulins, but also in various protein factors regulating both the immune system and the general metabolism of the body. Of great interest as factors regulating metabolism are low molecular weight fractions of proteins and peptides, which include the so-called transfer factors [2]. These are peptides with a molecular weight from 3500 Da to 6000 Da, which are inherent in all animals, are not species specific, they carry antigenic fragments and stimulate the activity of the immune system [3]. As is known, a cow gives from 5 to 10 liters of colostrum per milking, which significantly exceeds the needs of a calf [4], and the remaining amounts of colostrum can be used for industrial processing in order to obtain various biologically active compounds. Despite the fact that according to Chaudhary et.al. 2016 colostrum is “liquid gold” and has long been used in traditional medicine, it has not yet found proper use in modern industrial processing. This is due to a number of features and unresolved problems: the difficulty of storage and the peculiarity of processing; incomplete knowledge of its effect on the functional characteristics of an adult organism; instability and high individual variability of composition. A number of experts believe that the potential of biologically active compounds of colostrum, including its low molecular weight components, is not fully used [5]. In this regard, a part of the proteomic composition was studied, which includes proteins and peptides with a molecular weight from 4500 kDa to 9500 kDa, in different cows kept in the same farm, receiving the same feed, of the same breed and of the same age. To do this, fat was removed from fresh colostrum by repeated sequential centrifugation at 3000 g for 20 min, followed by casein precipitation at the isoelectric point. High molecular weight fractions of proteins were removed by membrane filtration; for this, filters with a pore diameter of 10 μm were used. The analysis of the obtained samples was carried out on a mass spectrometer Autoflex II LRF 20 “Bruker Daltonics” (Germany).
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Bovine Dialyzable Leukocyte Extract IMMUNEPOTENT CRP: Evaluation of Biological Activity of the Modified Product
Article
Full-text available
  • Apr 2021
Dialyzable leukocyte extracts are clinically used under different commercial names (IMMUNEPOTENT CRP®, IMMODIN®, Transferon®) to modulate the immune response altered by pathological conditions such as cancer, inflammation, and viral infections. The purpose of this study is to improve the production process of bovine dialyzable leukocyte extract without decreasing its biological activities (antioxidant, anti-inflammatory, and antitumoral). Our product modification consists of adding a dry heating step in the production process. In this study, we evaluated and compared the chemical composition (bromatological analysis), physical structure (infrared spectroscopy, X-ray diffraction, SEM, and zeta potential) and biological function of the dialyzable leukocyte extracts obtained from fresh and dry bovine spleens. Our results showed that the use of a drying step in the production process of the bovine dialyzable leukocyte extract (bDLE) did not affect its antioxidant and anti-inflammatory effects and it improved its antitumor properties. We suggest that this process modification could be applied to other biological products, such as dialyzable leukocyte extracts derived from other sources, in order to improve its functionality and formulation.
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Effect of splenic transfer factor on the development of intestinal mucosal barrier in laying hens
Article
  • Sep 2022
Background: The aim of this study is to investigate the effects of different doses of chicken spleen transfer factor (TF) on the structure of intestinal epithelial cells in different age groups. One-day-old White Leghorns laying hens were randomly divided into four groups-three groups were administered TF at different dosages (TF, 0.10 mL, TF, 0.25 mL, TF, 1.00 mL) and a fourth group was set as control (administered saline, 1.00 mL). Using H&E staining, high-throughput sequencing, Microbiota analysis, qPCR and Western blotting. Results: We measured the effects of different doses of TF on the following: intestinal mucosal epithelial tissue morphology, intestinal mucosal epithelial barrier-related gene expression profiles, intestinal epithelial tight junction gene protein levels. The collected data show that TF can improve the absorption of nutrients by increasing villus height and crypt depth and TF regulates intestinal flora disorders. Furthermore, we verified that the expression of the Claudin and Occludin tight junctions in between intestinal epithelial cells was increased with TF, this research is very important for focusing on the structure and gene expression of intestinal tissues. Conclusions: The results provide a scientific rationale for feeding and nutrition programs for green and healthy farming, as well as technical support to improve the production efficiency of the livestock and poultry breeding industry. This article is protected by copyright. All rights reserved.
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Interstitial transfer factor as adjuvant immunotherapy for experimental glioma
Article
Full-text available
Glioblastoma multiform (GBM) is the most common tumour of the central nervous system in humans. Unfortunately its prognosis is poor and because of the lack of efficacious therapies, immunotherapy is a potential treatment. Transfer factors (TF) are low molecular weight dialysable products extracted from immune cells which transmit the ability to express delayed-type hypersensitivity and cell mediated immunity from sensitized donors to nonimmnune recipients. In this study, we determined the efficacy of TF as immunotherapy to treat experimental glioblastoma. We used TF obtained from immunized swine. We evaluated different doses of intratumoral TF (product of 4x10(6), 8x10(5) and 1.6x10(5) cells). The best dose (product of 4x10(6) cells) of TF was also combined with carmustine for experimental therapy in rats with C6 malignant glioma. Modifications in peripheral blood T lymphocyte counts ( CD2+, CD4+, CD8+ and NK) were evaluated by flow cytometry. Cytokine expression in the tumour was assessed by RT-PCR and apoptosis was evaluated using the sub G0 method. Intratumoral TF reduced significantly the tumour size, and increased CD2+, CD4+, CD8+ and NK cell counts, it also increased the percentage of apoptotic tumour cells and the percentage of tumour tissue expressing Th1 cytokines. We observed an additive antitumoral effect when TF was combined with chemotherapy.
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Antigen-specific inducer factor in human leukocyte dialysates: a product of TH cells which binds to anti-V region and anti-la region antibodies
Article
  • Dec 1983
This chapter discusses the characterization of the moiety associated with suppressor activity in human dialysates of leukocyte extracts (DLE) prepared from immune donors. Within the crude dialysates exist both antigen-specific suppressor and as nonspecific suppressor factors. The antigen-specific suppressor factor can be readily separated from the nonspecific suppressor by dialysis and by dilution. The antigen-specific suppressor resides in the >3500 <12,000 D dialysis fraction, and the nonspecific suppressor resides in the <3500 D dialysis fraction. Additionally, nonspecific suppressor activity disappears upon dilution at a time when significant antigen-specific suppressor activity is still detectable at 1/8 and 1/16 of its original concentration. The absorption of this inducer-less immune DLE by specific antibody (paratope) results in the expression of inducer activity in this DLE. This suggests that some DLE may appear inactive as judged by the induction of cell-mediated immunity by virtue of excessive amounts of an antiparatopic-like inhibitor. The molecular identity of the inhibitor of immune DLE and the suppressor of immune lymphocytes remains to be determined.
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Characterization of a human lymphoblastoid cell line, LDV/7, used to replicate transfer factor and immune RNA
Article
  • Jan 1982
A lymphoblastoid cell line, LDV/7, a B-like cell line, was established several years ago and used for the replication of transfer factor and immune RNA in vitro. Chromosome analysis, morphological and cytochemical studies have shown that LDV/7 is a very heterogeneous cell line, growing in various nutrient media as a monolayer, and also in spinner culture. It is a non-EBV-producing cell line, although 90% of the cells are EBNA-positive. No active retro-virus infection was detectable; reverse transcriptase was nor present in these cells. Injection of LDV/7 cells into nude mice produces tumors which will eventually regress and the host shows resistance to a new challange. These studies did not provide an explanation for the ability of this cell line to replicate transfer factor and I-RNA.
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Prevention of herpes simplex virus type 1 fatal dissemination in primates with human transfer factor
Article
  • Dec 1976
This chapter elaborates the prevention of herpes simplex virus type 1 fatal dissemination in primates with human transfer factor (TF). The specificity of protection was evaluated by examining efficacy against another herpes group virus infection, Herpesvirus saimiri induced leukemia, in the same species of primate. Dialyzable TF was prepared and purified from the single donor. The studies demonstrate the efficacy of human TF in preventing death from herpes simplex virus type 1 induced fatal infection in an animal model. Pretreatment appeared necessary for protection because no animal survived who did not receive TF at least 3 days prior to challenge. Both animals who demonstrated positive cellular immune responses to HSV-1 after TF therapy and were then challenged, survived without ever being clinically ill. The limited number of animals, however, prevents too general an interpretation of results. The small blood volume of marmosets prevented more numerous determinations of in vitro lymphocyte blastogenesis during the course of TF therapy and disease in the other treatment groups, so only the 3 week pretreatment animals could be studied for conversion prior to viral challenge.
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Transfer Factor
Article
  • Dec 1969
This chapter reviews the extensive literature on various transfer factors involved in cellular immunity. This is a very enlightening review of an area of immunology from which much is expected to apply in the future. The methodology is partially worked out for obtaining transfer factor, as well as some of the other materials, in sufficient purity for chemical analysis, and further results in this area are awaited with great interest. Transfer factor began with the demonstration that cellular transfer of tuberculin hypersensitivity can be accomplished in humans using viable leukocytes obtained from sensitive donors. These observations led to the finding that leukocyte extracts are as effective as viable cells in the transfer of delayed hypersensitivity in humans that allowed the search for the identity of the material(s) responsible for transfer factor activity to begin. The term “transfer factor” is used in the chapter to designate the specific factor or factors in leukocytes responsible for the transfer of delayed hypersensitivity. Transfer factor is also used to describe either the active moiety residing in specifically sensitive, viable blood leukocytes or is applied to the equivalent activity liberated from living cells mechanically ( lysis, freeze-thawing ) or immunologically (interaction with specific antigen), as well as to the more purified low-molecular-weight preparation separated from subcellular constituents by dialysis and concentrated by lyophilization.
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The usefulness of transfer factor in asthma associated with frequent infections
Article
Fifteen patients underwent controlled trial with transfer factor for repeated infections and severe asthma. Marked decrease in respiratory infections and striking improvement in asthma resulted. The authors suggest that transfer factor may reconstitute immune function, thus representing a unique approach to severe asthma associated with frequent infections.
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Dialyzable transfer factor in the treatment of human osteosarcoma: an analytic review
Article
  • Feb 1976
In conclusion, then, we would answer the seven questions raised earlier concerning transfer factor as follows: Certianly, as shown by clinical results, it does exist. It does have a definite immunologic effect in humans, boosting cell-mediated immunity, as shown by a rise in the level of active T cells. Its clinical effects have been demonstrated repeatedly, and it should become useful in still other clinical situations as further research provides more effective therapeutic modalities. Transfer factor from selected donors appears to provide prophylaxis against metastasis when administered to osteosarcoma patients with no clinically evident metastases at the time of surgical removal of the primary tumor; whether this treatment is superior to chemotherapeutic prophylaxis is conjectural and controversial. Its mechanism of action has not been demonstrated as yet, although many theories exist. The best evidence is that the effects are both specific and nonspecific. It appears to be produced by T lymphocytes. The exact nature of the substance we call "transfer factor" remains to be elucidated. Further research should provide more conclusive answers to these questions.
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